Peripheral inflammation alters N-arachidonoylphosphatidylethanolamine (20:4-NAPE) induced modulation of nociceptive spinal cord synaptic transmiss
Author(s)
Type
Journal Article
Abstract
Background and Purpose
Endocannabinoids play an important role in modulati
ng spinal nociceptive signalling, crucial
for the development of pain. The cannabinoid recept
or 1 (CB1) and the transient receptor
potential cation channel subfamily V member 1 (TRPV
1) are both activated by the
endocannabinoid anandamide that is a product of bio
synthesis from the endogenous lipid
precursor N1arachidonoylphosphatidylethanolamine (2
0:41NAPE). Here we are first to report
CB1 receptor1 and TRPV11mediated effects of 20:41NA
PE application on spinal synaptic
transmission in control and inflammatory conditions
.
Experimental Approach
Spontaneous (sEPSCs) and dorsal root stimulation1ev
oked (eEPSCs) excitatory postsynaptic
currents from superficial dorsal horn neurons in ra
t spinal cord slices were assessed.
Peripheral inflammation was induced by carrageenan.
Anandamide concentration was
assessed by mass spectrometry.
Key Results
Application of 20:41NAPE increased anandamide conce
ntration
in vitro
. 20:41NAPE (20 μM)
decreased sEPSCs frequency and eEPSCs amplitude in
control and inflammatory conditions.
The inhibitory effect of 20:41NAPE was sensitive to
CB1 antagonist PF514273 (0.2 μM) in
both conditions, but to the TRPV1 antagonist SB3667
91 (10 μM) only after inflammation.
After inflammation 20:41NAPE increased sEPSCs frequ
ency in the presence of PF514273 and
this increase was blocked by SB366791.
Conclusions and Implications
While 20:41NAPE treatment produced an inhibitory ef
fect on excitatory synaptic transmission
in both naive and inflammatory conditions, peripher
al inflammation altered the underlying
mechanisms. Our data indicate that 20:41NAPE applic
ation induced mainly CB1 receptor1
mediated inhibitory effects in naive animals while
TRPV11mediated mechanisms were also
involved after inflammation. Increasing anandamide
levels for analgesic purposes by applying
substrate for its local synthesis may be superior to systemic anandamide application or
inhibition of its degradation.
Endocannabinoids play an important role in modulati
ng spinal nociceptive signalling, crucial
for the development of pain. The cannabinoid recept
or 1 (CB1) and the transient receptor
potential cation channel subfamily V member 1 (TRPV
1) are both activated by the
endocannabinoid anandamide that is a product of bio
synthesis from the endogenous lipid
precursor N1arachidonoylphosphatidylethanolamine (2
0:41NAPE). Here we are first to report
CB1 receptor1 and TRPV11mediated effects of 20:41NA
PE application on spinal synaptic
transmission in control and inflammatory conditions
.
Experimental Approach
Spontaneous (sEPSCs) and dorsal root stimulation1ev
oked (eEPSCs) excitatory postsynaptic
currents from superficial dorsal horn neurons in ra
t spinal cord slices were assessed.
Peripheral inflammation was induced by carrageenan.
Anandamide concentration was
assessed by mass spectrometry.
Key Results
Application of 20:41NAPE increased anandamide conce
ntration
in vitro
. 20:41NAPE (20 μM)
decreased sEPSCs frequency and eEPSCs amplitude in
control and inflammatory conditions.
The inhibitory effect of 20:41NAPE was sensitive to
CB1 antagonist PF514273 (0.2 μM) in
both conditions, but to the TRPV1 antagonist SB3667
91 (10 μM) only after inflammation.
After inflammation 20:41NAPE increased sEPSCs frequ
ency in the presence of PF514273 and
this increase was blocked by SB366791.
Conclusions and Implications
While 20:41NAPE treatment produced an inhibitory ef
fect on excitatory synaptic transmission
in both naive and inflammatory conditions, peripher
al inflammation altered the underlying
mechanisms. Our data indicate that 20:41NAPE applic
ation induced mainly CB1 receptor1
mediated inhibitory effects in naive animals while
TRPV11mediated mechanisms were also
involved after inflammation. Increasing anandamide
levels for analgesic purposes by applying
substrate for its local synthesis may be superior to systemic anandamide application or
inhibition of its degradation.
Date Issued
2018-06-01
Date Acceptance
2017-04-27
Citation
British Journal of Pharmacology, 2018, 175 (12), pp.2322-2336
ISSN
1476-5381
Publisher
Wiley
Start Page
2322
End Page
2336
Journal / Book Title
British Journal of Pharmacology
Volume
175
Issue
12
Copyright Statement
© 2017 The British Pharmacological Society
Sponsor
Wellcome Trust
British Journal of Anaesthesia
Commission of the European Communities
Grant Number
081637/Z/06/Z
DSAN_P20272
254661
Subjects
1115 Pharmacology And Pharmaceutical Sciences
Pharmacology & Pharmacy
Publication Status
Published
Date Publish Online
2017-05-05